Redirecting the Rules of Attraction in Fruit Flies

Many previous studies have identified differences in brain structure between the sexes. However this study, published in Cell, is the first description in any animal of a specific change in nerve cell wiring that reroutes information between male and female brains.

Sex pheromones are chemicals that allow male and female animals to communicate by smell, typically provoking different responses in the two sexes. For example in fruit flies, a male sex pheromone called cVA can stimulate females to mate with a male, while repelling other males at the same time. What changes in the brain result in male and female flies interpreting the same pheromone signal in very different ways?

The team first identified and labelled two groups of nerve cells inside the fly brain that respond to pheromones using a green fluorescent protein. One group of nerve cells responded to pheromone only in male brains, while the second group responded only in females. This difference in response depended on a changeover switch that rerouted incoming pheromone information to different target cells.

In further experiments the team were able to make a small number of nerve cells male in an otherwise female brain. Manipulating the sex of the nerve cells, helped to pin point the location and the gene responsible for the ‘switch’, reversing the fly’s response to pheromones. The so-called ‘fruitless’ gene controlling this switch had previously been shown to control fruit flies’ sexual behaviour but exactly how it could achieve this through changes in brain wiring was unknown.

Dr Greg Jefferis who led the study at the MRC Laboratory of Molecular Biology said: “Arguably the biggest challenge in biology today is to understand how the pattern of connections between individual nerve cells allows the brain to process and store information and respond to the outside world. Given the huge complexity of human or even mouse brains, there is great interest in trying to understand basic principles in simpler model systems such as the fruit fly.

Looking at the differences between the male and female brains of a species allows us to focus our efforts on wiring differences that can change behaviour. Until now it has proven very difficult to identify specific and reproducible differences in brain wiring and understand how they could alter the flow of information between male and female brains. This is what we have now shown in flies. We suspect that the same principle will apply across many species, including mammals.”

Dr Hugh Pelham, director of the MRC Laboratory of Molecular Biology. “The MRC Laboratory of Molecular Biology has a well-founded reputation for contributing to some of the world’s most important biological questions by detailed investigation starting at the molecular level. Investing in science that opens up research avenues from simple brains to more complex ones is paving the way for a far greater understanding of our own brains in health and disease.”